{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T19:39:01Z","timestamp":1772221141006,"version":"3.50.1"},"reference-count":87,"publisher":"Public Library of Science (PLoS)","issue":"3","license":[{"start":{"date-parts":[[2025,3,18]],"date-time":"2025-03-18T00:00:00Z","timestamp":1742256000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001695","name":"Japan Science and Technology Corporation","doi-asserted-by":"publisher","award":["JPMJMS2021"],"award-info":[{"award-number":["JPMJMS2021"]}],"id":[{"id":"10.13039\/501100001695","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000646","name":"Japan Society for the Promotion of Science London","doi-asserted-by":"publisher","award":["21K06124,24K09248"],"award-info":[{"award-number":["21K06124,24K09248"]}],"id":[{"id":"10.13039\/501100000646","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>\n                    Late-onset Alzheimer\u2019s disease (AD) is a typical type of dementia for which therapeutic strategies have not yet been established. The database of the Rush Alzheimer\u2019s Disease study by the ENCODE consortium contains transcriptome and various epigenome data. Although the Rush AD database may contain a satisfactory amount of data for women, the amount of data for men remains insufficient. Here, based on an analysis of publicly available data from female patients, this study found that AD pathology appears to be nonuniform; AD patients were divided into several groups with differential gene expression patterns, including those related to cognitive function. First, cluster analysis was performed on individuals diagnosed with \u201cNo Cognitive Impairment (NCI),\u201d \u201cMild Cognitive Impairment (MCI),\u201d and \u201cAlzheimer\u2019s Disease (AD)\u201d stages in clinical trials using gene expression, and multiple substages were identified across AD progression. The epigenome data, in particular genome-wide H3k4me3 distribution data, also supported the existence of multiple AD substages. However,\n                    <jats:italic>APOE<\/jats:italic>\n                    gene polymorphisms of individuals seemed to not correlate with disease stage. An inference of adjacency networks among substages, evaluated via partition-based graph abstraction using the gene expression profiles of individuals, suggested the possibility of multiple typical disease progression pathways from NCI to different AD substages through various MCI substages. These findings could refine biomarker discovery or inform personalized therapeutic approaches.\n                  <\/jats:p>","DOI":"10.1371\/journal.pone.0313733","type":"journal-article","created":{"date-parts":[[2025,3,18]],"date-time":"2025-03-18T13:23:42Z","timestamp":1742304222000},"page":"e0313733","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Potential multiple disease progression pathways in female patients with Alzheimer\u2019s disease inferred from transcriptome and epigenome data of the dorsolateral prefrontal cortex"],"prefix":"10.1371","volume":"20","author":[{"given":"Kousei","family":"Honda","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0778-021X","authenticated-orcid":true,"given":"Akinori","family":"Awazu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2025,3,18]]},"reference":[{"issue":"2","key":"pone.0313733.ref001","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1001\/archpsyc.63.2.168","article-title":"Role of genes and environments for explaining Alzheimer disease","volume":"63","author":"M Gatz","year":"2006","journal-title":"Arch Gen Psychiatry"},{"key":"pone.0313733.ref002","volume-title":"Global action plan on the public health response to dementia 2017\u20132025","author":"World Health 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